TY - JOUR
T1 - α1-giardin based live heterologous vaccine protects against Giardia lamblia infection in a murine model
AU - Jenikova, Gabriela
AU - Hruz, Petr
AU - Andersson, Mattias K.
AU - Tejman-Yarden, Noa
AU - Ferreira, Patricia C D
AU - Andersen, Yolanda S.
AU - Davids, Barbara J.
AU - Gillin, Frances D.
AU - Svärd, Staffan G.
AU - Curtiss, Roy
AU - Eckmann, Lars
N1 - Funding Information:
This work was supported by NIH grants DK35108 , DK80506 , AI60557 , and AI56289 . M.K.A. was supported by the Swedish Research Council and the Sweden-America Foundation . P.C.D.F. was supported by a student fellowship from FAPESP (São Paulo Reasearch Foundation) . We thank Gregory J. Botwin and Soo Young Wanda for excellent technical support.
PY - 2011/11/28
Y1 - 2011/11/28
N2 - Giardia lamblia is a leading protozoan cause of diarrheal disease worldwide, yet preventive medical strategies are not available. A crude veterinary vaccine has been licensed for cats and dogs, but no defined human vaccine is available. We tested the vaccine potential of three conserved antigens previously identified in human and murine giardiasis, α1-giardin, α-enolase, and ornithine carbamoyl transferase, in a murine model of G. lamblia infection. Live recombinant attenuated Salmonella enterica Serovar Typhimurium vaccine strains were constructed that stably expressed each antigen, maintained colonization capacity, and sustained total attenuation in the host. Oral administration of the vaccine strains induced antigen-specific serum IgG, particularly IgG 2A, and mucosal IgA for α1-giardin and α-enolase, but not for ornithine carbamoyl transferase. Immunization with the α1-giardin vaccine induced significant protection against subsequent G. lamblia challenge, which was further enhanced by boosting with cholera toxin or sublingual α1-giardin administration. The α-enolase vaccine afforded no protection. Analysis of α1-giardin from divergent assemblage A and B isolates of G. lamblia revealed >97% amino acid sequence conservation and immunological cross-reactivity, further supporting the potential utility of this antigen in vaccine development. Together. These results indicate that α1-giardin is a suitable candidate antigen for a vaccine against giardiasis.
AB - Giardia lamblia is a leading protozoan cause of diarrheal disease worldwide, yet preventive medical strategies are not available. A crude veterinary vaccine has been licensed for cats and dogs, but no defined human vaccine is available. We tested the vaccine potential of three conserved antigens previously identified in human and murine giardiasis, α1-giardin, α-enolase, and ornithine carbamoyl transferase, in a murine model of G. lamblia infection. Live recombinant attenuated Salmonella enterica Serovar Typhimurium vaccine strains were constructed that stably expressed each antigen, maintained colonization capacity, and sustained total attenuation in the host. Oral administration of the vaccine strains induced antigen-specific serum IgG, particularly IgG 2A, and mucosal IgA for α1-giardin and α-enolase, but not for ornithine carbamoyl transferase. Immunization with the α1-giardin vaccine induced significant protection against subsequent G. lamblia challenge, which was further enhanced by boosting with cholera toxin or sublingual α1-giardin administration. The α-enolase vaccine afforded no protection. Analysis of α1-giardin from divergent assemblage A and B isolates of G. lamblia revealed >97% amino acid sequence conservation and immunological cross-reactivity, further supporting the potential utility of this antigen in vaccine development. Together. These results indicate that α1-giardin is a suitable candidate antigen for a vaccine against giardiasis.
KW - Animal models
KW - Giardiasis
KW - Live oral vaccines
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U2 - 10.1016/j.vaccine.2011.09.126
DO - 10.1016/j.vaccine.2011.09.126
M3 - Article
C2 - 22001876
AN - SCOPUS:81955164754
SN - 0264-410X
VL - 29
SP - 9529
EP - 9537
JO - Vaccine
JF - Vaccine
IS - 51
ER -